In this study, we (three independent research groups) evaluated the binding characteristics of various published RNA and DNA aptamers targeting the spike protein of the SARS-CoV-2 virus. Employing different techniques we discovered discrepancies in the reported specificity and affinity among several of the published aptamers and want to underline the importance of standardized methods, the impact of biophysical techniques, and the controls used for aptamer characterization.
We have developed and engineered a serum-stable RNA aptamer specific for SARS-CoV-2 spike protein. We further show that scaffolding three aptamers together increases the binding efficiency to the low picomolar range and enables very efficient neutralization of SARS-CoV-2 infection in cells. The aptamer also shows high affinity for spike protein from variants of concern. Due to its small size and chemical stability, our aptamer holds potential as an alternative to antibodies and nanobodies targeting spike protein.
